The prospect of a microwave applicator fully dedicated to continuous flow
chemistry may offer many advantages over traditional heating methods, such as fast and
controlled heating at high temperatures, as well as a higher level of safety regarding
explosive reagents and pressure-producing reactions.
Synthetic protocols are hereby developed with a unique system utilizing a nonresonant
microwave heating applicator purpose-built for continuous flow that heats an
entire reactor without pronounced hot and cold spots, allowing method optimization in
small scale and subsequent scale-out without scale-up translation. With a pressure
resistance of up to 50 bars and volumes spanning the range of 160 µL (1 mm ID) to 6
mL (6 mm ID), the consumable glass reactors employed by the system allow a variety
of flow regimes, scales, as well as superheating of solvents.
The technology is demonstrated with method optimization and scale-out of classic
organic reactions including palladium-catalyzed organic transformations, synthesis of a
bioactive M. tuberculosis proteasome inhibitor, and Fischer indole synthesis with a
residence time of only 20 seconds, producing 34 grams of compound per hour (199
mmol/hour) with an isolated yield of 85%.

The prospect of a microwave applicator fully dedicated to continuous flow
chemistry may offer many advantages over traditional heating methods, such as fast and
controlled heating at high temperatures, as well as a higher level of safety regarding
explosive reagents and pressure-producing reactions.
Synthetic protocols are hereby developed with a unique system utilizing a nonresonant
microwave heating applicator purpose-built for continuous flow that heats an
entire reactor without pronounced hot and cold spots, allowing method optimization in
small scale and subsequent scale-out without scale-up translation. With a pressure
resistance of up to 50 bars and volumes spanning the range of 160 µL (1 mm ID) to 6
mL (6 mm ID), the consumable glass reactors employed by the system allow a variety
of flow regimes, scales, as well as superheating of solvents.
The technology is demonstrated with method optimization and scale-out of classic
organic reactions including palladium-catalyzed organic transformations, synthesis of a
bioactive M. tuberculosis proteasome inhibitor, and Fischer indole synthesis with a
residence time of only 20 seconds, producing 34 grams of compound per hour (199
mmol/hour) with an isolated yield of 85%.